Mayo Clinic

ROCKVILLE, Md. and SUZHOU, China, April 7, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, age-related diseases, and chronic hepatitis B (CHB), announced today that it releases the latest results from three preclinical studies of its novel drug candidates olverembatinib, MDM2-p53 inhibitor alrizomadlin (R&D Code: APG-115), FAK/ALK/ROS1 tyrosine kinase inhibitor APG-2449, and embryonic ectoderm development (EED) inhibitor APG-5918, at the 2024 American Association of Cancer Research Annual Meeting (AACR 2024). This year's AACR annual meeting will be held from April 5-10 2024, in San Diego, California, USA. "We are pleased to present the preclinical research data of four assets in our pipeline at the AACR 2024. The results provided essential support for the potential clinical development and therapeutic combinations of these compounds in SDH-deficient neoplasms, prostate cancer, and ovarian cancer," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moving forward, we will continue to advance these programs toward the clinical stage in order to bring more treatment options to patients in need." The details of these three preclinical studies are as follows: Olverembatinib, a novel multikinase inhibitor, demonstrates superior antitumor activity in succinate dehydrogenase (SDH)-deficient neoplasms Abstract#: 1971 Time: Monday April 8, 2024, 9:00 AM - 12:30 PM (Pacific Time) Introduction: Succinate dehydrogenase (SDH) – deficient (dSDH) neoplasms are identified by the loss of immunohistochemical expression of SDHB due to the bi-allelic inactivation of any of the four components of mitochondrial SDH complex (SDH A-D). Succinate accumulation, due to SDH deficiency, is involved in tumorigenesis of different types of cancers including gastrointestinal stromal tumor (GIST), paraganglioma, pheochromocytoma, renal cell carcinoma, pituitary adenomas, and pancreatic neuroendocrine tumors. The prognosis of patients with dSDH neoplasia, especially GIST, is poor and approved tyrosine kinase inhibitors (TKIs) have limited efficacy. There is a high unmet medical need for these patients. Olverembatinib, a novel multi-kinase inhibitor, targets a broad spectrum of kinases and has demonstrated promising efficacy in dSDH GIST patients in an ongoing phase I clinical trial. In this study, we assessed antitumor effects of olverembatinib in preclinical models of dSDH cancers and dSDH GIST primary tumor cells, and explored potential mechanisms of action. Conclusions: Olverembatinib showed superior anti-tumor activity in dSDH cell lines in vitro and human dSDH GIST primary tumor cells ex vivo. Olverembatinib, as a multi-target kinase inhibitor, exerted antitumor effects by modulating multiple signaling pathways including hypoxia, angiogenesis, apoptosis, proliferation, and survival, which are involved in tumorigenesis of dSDH cancers. Olverembatinib demonstrated more potent in vivo antitumor activity in mice bearing PC12#5F7 (SDHB KD) xenograft tumors than other TKIs. Western blot analysis in tumor tissues collected from mice further confirmed the modulation of the signal pathways by olverembatinib observed in cell lines. In summary, the results provide a rationale for future clinical development of olverembatinib in dSDH cancers. Embryonic ectoderm development (EED) inhibitor APG-5918 (EEDi-5273) and MDM2 inhibitor alrizomadlin (APG-115) synergistically inhibit tumor growth in preclinical models of prostate cancer (PCa) Abstract#: 3223 Time: Monday April 8, 2024, 1:30 PM - 5:00 PM (Pacific Time) Introduction: Prostate cancer (PCa) is one of the most frequently diagnosed malignancies among elderly males. Androgen deprivation therapy (ADT) with or without androgen receptor (AR) inhibitors is widely used as initial treatment for advanced PCa. However, most ADT-treated patients eventually develop castration-resistant prostate cancer (CRPC), which is in urgent need of novel therapies. Polycomb repressive complexes 2 (PRC2) dysregulation is common in PCa and correlates with poor prognosis. PRC2 mediates histone H3 lysine 27 tri-methylation (H3K27me3), a repressive epigenetic marker for gene transcription. embryonic ectoderm development (EED), a PRC2 core component, is crucial for histone methyltransferase activity through direct binding to H3K27me3. MDM2, a negative regulator of the tumor suppressor p53, is frequently amplified or overexpressed in PCa, and associated with poor clinical outcomes and metastasis. The aim of this study was to evaluate antitumor activity and molecular mechanisms of the investigational, clinical-stage EED inhibitor APG-5918/EEDi-5273 and MDM2 selective inhibitor alrizomadlin (APG-115) in PCa preclinical models Conclusions: In PCa preclinical models, the combination of APG-5918 and alrizomadlin synergistically inhibited cellular proliferation and induced cellular apoptosis. APG-5918 in combination with alrizomadlin synergistically enhanced antitumor activity in PCa xenograft models in vivo. Mechanistically, PD analysis revealed that APG-5918 downregulated the oncogenic DNA methylation factors (UHRF1, DNMT1) and histone methylation marker H3K27me3. Alrizomadlin markedly downregulated UHRF1 and DNMT1, and upregulated p53 and p21 expression. Combined treatment further enhanced downregulation of DNMT1, UHRF1, cell cycle pathway proteins (pRb, CDK6), antiapoptotic protein MCL-1, and synergistically increased cleavage of PARP-1, a marker of apoptosis. Therefore, the findings provide a scientific rationale for future clinical development of APG-5918 and alrizomadlin to treat patients with PCa. APG-2449, a novel focal adhesion kinase (FAK) inhibitor, inhibits metastasis and enhances the antitumor efficacy of PEGylated liposome doxorubicin (PLD) in epithelial ovarian cancer (EOC) Abstract#: 4569 Time: Tuesday April 9, 2024, 9:00 AM - 12:30 PM (Pacific Time) Introduction: Ovarian cancer is among the leading causes of cancer-related death in women, and most cases are diagnosed at later stages with distant metastasis. FAK overexpression or activation occurs in a substantial proportion of epithelial ovarian cancers (EOCs) and is predictive of poor clinical outcomes. FAK plays an important role in cell migration and chemoresistance, rendering FAK inhibition a promising treatment approach to reduce metastasis of tumor cells and sensitize them to chemotherapy. FAK is therefore emerging as a potential treatment target. The aim of this study was to evaluate the antitumor efficacy of investigational APG-2449, a novel FAK inhibitor, combined with PLD, a commonly used chemotherapy, in relapsed or refractory ovarian cancer. Conclusions: APG-2449 combined with doxorubicin showed synergistic antiproliferative effects in both platinum-resistant and platinum-sensitive ovarian cancer cell lines. FAK inhibition via APG-2449 alone attenuated migration of ovarian cancer cells in a dose-dependent manner. APG-2449 in combination with PLD showed enhanced antitumor activity in platinum-resistant OVCAR-3 ovarian cancer CDX model. The combination regimen prolonged ascites-free and survival times in the ID8-Luc peritoneal syngeneic model. These promising results support the future clinical development of this combination treatment for ovarian cancer. About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma

Yesterday, in part one of our in-depth interview with Dr. Brian Hasselfeld of Johns Hopkins Medicine, the senior medical director of digital health and innovation and associate director of Johns Hopkins inHealth, discussed the role of artificial intelligence in healthcare overall. Today, Hasselfeld, who also is a primary care physician in internal medicine and pediatrics at Johns Hopkins Community Physicians, turns his focus to Johns Hopkins itself, where he and a number of teams throughout the organization have implemented AI in ambient scribing and patient portal applications. They're working with EHR giant Epic on deploying AI for chart summarization – a major step forward. Q. Let's turn to AI at Johns Hopkins Medicine. You are using ambient scribe technology. How does this work in your workflows and what kinds of outcomes are you seeing? A. Certainly a very topical space. We're seeing a number of products taking a wide range of strategies. We're similar to many that have taken some early moves in this space, recognizing technology really hasn't done what it's supposed to do in healthcare. Arguably, most of the data would say, at least to the clinician, technology has done more harm in some ways, at least to our own workflows and experience in healthcare. So, we're trying to think about some of those pieces where we can move technology back to the center and make it more enjoyable. Again, many have acknowledged the documentation burden that sits on top of our clinicians with the explosion of EHR content, both by regulatory requirements and general workflow across many major systems. So, for most of our systems that have picked up on ambient AI , a listening device, the ambient part of it is listening to a clinical encounter, whether it be an outpatient visit, an ER history or inpatient rounds. And on the back-end, the AI tool, usually what's now known as a large language model, such as GPT, then takes the spoken word between the multiple parties and constructs it into a new generative paragraph. It's using the actual function of those large language models to generate a paragraph of content, usually then around a specific prompt. Given that model, "Please write a history based on this medical background." And we've deployed that currently across a number of ambulatory or outpatient clinics, across a couple of different areas of specialty, currently with our first product and likely thinking about how we use more than one product to understand the different levels of functionality. I myself just had clinic this morning and was fortunate enough to be using the ambient AI technology using a device, my own smartphone, with our EHR on the phone, and be able to launch the ambient AI product, which listens to the encounter and generates a draft note, which, of course, I'm responsible for and need to review myself and edit to ensure clinical accuracy. It's really making that clinical interaction much better. The ability to take the hands off the keyboard, look directly at the patient, and have an open conversation about a very intimate topic, their own personal health, and really taking the eyes from the computer and back to the patient, in my mind, is the main benefit so far. Q. Johns Hopkins Medicine also is using AI for patient portal message draft replies. Please explain how physicians and nurses use this and the kinds of outcomes they achieve. A. This enterprise tool is out to early users. It is probably well-known now to many who follow HIMSS Media content that patient emails or in-basket messages, messages generated through the patient portal , have exploded through the pandemic. Here at Hopkins, we saw a nearly 3X increase in the number of messages sent by patients to our clinicians from pre-COVID in late 2019 to our run-rate that we see now. And some of that's a really good thing. We want our patients to be engaged with us. We want to know when they're feeling well or not well, and help be able to triage. But again, the clinical workflow, including payment models and clinical care models, is not built for this constant communication, this constant contact. It's built around visits. We did a well-intentioned thing, increasing connectivity with our patients. It's a very easy modality, something we all do every day – email and text. We're used to communicating what we would call asynchronously or through written communication. But we really didn't change the other side of it. The unintended consequence was dumping all that volume onto an unchanged clinical practice system. Now, all of us are trying to figure out how we accelerate improvement in that meaningful area of clinician burnout while maintaining the benefit to our patients in having freer contact with their clinical team. So, a message comes in. Some things are excluded, especially if they have attachments and things like that, as those types of messages are more difficult to interpret. And once the message lands at a clinical care team member, those that have access to the pilot deployment of the AI draft responses will see an option to select a draft response based on the content of the original message, then see the large language model's draft response, based on some instructions given to it to try to interpret it in an appropriate way. I can choose, as a clinician, to start with that draft or start with a blank message. Stanford just put out a paper on this, and articulates some of the pros and cons quite well, that one of the benefits is decreased cognitive burden on trying to think about responses for very routine types of messages. We have also seen that clinicians who have picked up this tool and use it on a regular basis are definitely expressing a decreased in-basket burnout and clinician wellness metric. But at the same time, I think minimal time is saved right now because the draft responses are only really applicable and really useful to the patient message a minority of the time. In the Stanford published paper, it was 20% of the time. We see our clinics ranging from low single-digit percentage to 30-40%, depending on the type of user, but still far less than half. The tool is not perfect, the workflow is not perfect, and it's going to be part of that rapid but iterative process to figure out how we apply these tools to the most useful scenarios at this point. Q. I understand Johns Hopkins Medicine is working on chart summarization via AI, with an initial emphasis on inpatient hospital course summary. How will AI work here and what are your expectations? A. Of all the projects, this one is in its earliest phases. It's a good example of the differences in application of the technology across the continuum of care and the depth of the problem being tackled. In the previous examples, ambience and in-basket draft replies, we're really working on a very concise transactional component to the clinical continuum. The single visit and its associated discussion, the single message and drafting a response. That's very contained data. When we start to think about that broader topic of chart summarization, the sky's the limit, unfortunately or fortunately, in the problem to be addressed – the depth of data that needs to be understood. And again, that needs to be extracted from unstructured to structured. Really, the work we as clinicians do every time we interact with the chart, we move through the chart in various ways, we extract what we feel we need to know, and we re-summarize. It's a complex task. We are trying to work in the most targeted area, during an inpatient admission, you are essentially more time-bound than in other versions of chart summarization. In outpatient, you may have to chart summarize 10 years of information depending on why you're coming to that clinician or your reason for a visit. I had a new patient earlier today. I needed to know everything about their medical history. That's a massive chart summarization task. In inpatient, we have an opportunity to create some time-bound around what needs to be summarized. So, not even starting at the entirety of everything about the hospitalization – which actually can include reason for admission, which then can backtrack into the rest of the chart. Inside of an admission, we have day-to-day progression of your journey through your hospital stay and interval change. Those are addressed in daily progress notes, in handouts between clinical teams. And we can narrow down the information to be summarized to the things that change and happen from yesterday to today, even though it's a lot of potential things – images, labs, notes from the primary team, notes from the consultant, notes from the nursing team. It is much more time-bound and still injects meaningful efficiency to the inpatient teams, and certainly identifies a well-known area of risk, which is handoff. Anytime your clinical team changes during your inpatient stay, which is frequent as we don't ask clinicians to work 72 hours straight in most cases, then we have an opportunity to help support those areas of high-risk handoff. So, trying to range-bound, and even here in this very range-bound case, there is a lot of work to be done to get a potential tool ready for actual use in the clinical workflow , given, quite frankly, the breadth and depth of data that is available. We just started this discovery journey, working with our EHR partners at Epic, and are looking forward to seeing what might be possible here. To watch a video of this interview with BONUS CONTENT not in this story, click here . Editor's Note: This is the seventh in a series of features on top voices in health IT discussing the use of artificial intelligence in healthcare. To read the first feature, on Dr. John Halamka at the Mayo Clinic, click here . To read the second interview, with Dr. Aalpen Patel at Geisinger, click here . To read the third, with Helen Waters of Meditech, click here . To read the fourth, with Sumit Rana of Epic, click here . To read the fifth, with Dr. Rebecca G. Mishuris of Mass General Brigham, click here . And to read the sixth, with Dr. Melek Somai of the Froedtert & Medical College of Wisconsin Health Network, click here . Follow Bill's HIT coverage on LinkedIn: Bill Siwicki Email him: bsiwicki@himss.org Healthcare IT News is a HIMSS Media publication.

TARA-002 demonstrated a complete response rate of 43% at three months in BCG-Unresponsive/Experienced patients in ongoing NMIBC programTARA-002 demonstrated a complete response rate of 63% at three months in CIS-only patients in ongoing NMIBC programTARA-002 demonstrated a favorable safety and tolerability profile with no Grade 3 or greater treatment-related adverse eventsPreliminary data from six-month evaluable patients in ADVANCED-2 trial of TARA-002 in NMIBC expected in 2H 2024 NEW YORK, April 05, 2024 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced positive data from three-month evaluable carcinoma in situ (CIS) patients treated across its ongoing clinical program of TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-Unresponsive, BCG-Experienced and BCG-Naïve patient populations. “These promising three-month results support the continued development of TARA-002 for patients with NMIBC for whom there are currently limited treatment options,” said Timothy Lyon, M.D., Associate Professor of Urology and the Urology Residency Program Director at Mayo Clinic in Florida, and TARA-002 study investigator. “Given our understanding that up to half of patients treated with intravesical immune therapies that do not initially respond can be salvaged with repeat induction, there is reason to believe that the promising three-month response rates shared today could be further improved through reinduction with TARA-002. This encouraging anti-tumor activity coupled with a favorable safety profile and mode of administration that is both convenient and familiar to urologists indicates that, if confirmed in future studies, TARA-002 could potentially play a meaningful role in NMIBC treatment in the future.” Enrollment continues in the Company’s ADVANCED-2 Phase 2 clinical trial of TARA-002 in patients with high-grade NMIBC with BCG-Unresponsive CIS and BCG-Naïve CIS. The ADVANCED-2 trial design incorporates both reinduction and maintenance dosing. The Company expects to share preliminary results from a pre-planned risk-benefit analysis of the ADVANCED-2 trial in ten patients, who are six-month evaluable in the second half of 2024. “We are highly encouraged by these early results observed in these three-month evaluable patients across our ADVANCED-1 and ADVANCED-2 clinical trials, which clearly demonstrate TARA-002’s activity in both BCG-Unresponsive and BCG-Naïve patients. We look forward to sharing data from post-reinduction, six-month evaluable patients in our ADVANCED-2 trial in the second half of 2024,” said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. Overview of Three-Month Evaluable Data Data reported today highlight the potential of TARA-002 in patients with NMIBC. Data were derived from three-month evaluable NMIBC patients with CIS pooled across the Company’s ADVANCED-1 Phase 1a, Phase 1b-expansion and ADVANCED-2 Phase 2 trials of TARA-002 in patients with high-risk NMIBC, including BCG-Unresponsive, BCG-Experienced and BCG-Naïve patients. The overall three-month complete response (CR) rate prior to reinduction for 16 evaluable patients treated across the three trials with varying BCG status was 38% (6/16), with a CR rate of 63% (5/8) in CIS-only patients and 13% (1/8) in patients with CIS +Ta/T1. The Company believes that reinduction and planned enhancements to dosing and administration will lead to an increased CR rate at six months in patients who did not achieve a CR at three months, as reinduction with other immune agents in NMIBC patients with CIS has demonstrated a 30%-50% salvage rate. The Company plans to explore additional dosing cohorts, which may prove effective in patients who might benefit. Three Month Evaluable Patients # Patients# of CRsCR % BCG-Unresponsive/ ExperiencedCIS-only6350% CIS +Ta/T11--% 7343% BCG-Naïve CIS-only22100% CIS +Ta/T17114% 9333% 16638% By Stage of Disease at Baseline CIS-only8563% CIS +Ta/T18113% 16638% By Study Phase 1a3133% Phase 1b-EXP8338% Phase 2 Naïve5240% 16638% The majority of reported adverse events were Grades 1 and 2 across all dose levels, and treatment emergent adverse events (TEAEs), as assessed by study investigators, were in line with typical responses to bacterial immunopotentiation, and included fatigue, headache, fever, and chills. The most common urinary symptoms were urinary urgency, urinary frequency, urinary tract pain/burning, incomplete emptying, and bladder spasm. Most bladder irritations resolved soon after administration or in a few hours to a few days. “TARA-002 is a broad spectrum immunopotentiator with a similar mechanism of action as the standard of care, BCG. Because TARA-002 is an inactivated bacteria, there are no special dosing and administration protocol requirements, which makes it ideal for administration in the community urology practice setting,” said Gautam Jayram, MD., Director, Advanced Therapeutics Center, Urology Associates PC in Nashville and TARA-002 study investigator. “I am encouraged by the early three-month data in a challenging disease state and look forward to continued participation in the TARA-002 clinical program.” NMIBC Clinical Program The ADVANCED-1 expansion trial is evaluating intravesical TARA-002 at the 40KE1 dose in up to 12 NMIBC patients with CIS and CIS +Ta/T1, including BCG-Unresponsive, BCG-Naïve, and BCG-Experienced patient populations. The primary endpoint is safety and complete response (CR) rate at the preliminary three-month assessment timepoint. The Phase 2 open-label ADVANCED-2 trial is assessing intravesical TARA-002 in at least 102 NMIBC patients with CIS (± Ta/T1) who are BCG-Unresponsive (n=75-100) and BCG-Naïve (n=27). The BCG-Unresponsive cohort has been designed to be registrational aligned with the FDA’s 2018 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry. Trial subjects receive an induction course of six weekly intravesical instillations, followed by either reinduction (if eligible) or maintenance for up to 24 months. Two additional exploratory cohorts will be added to the ADVANCED-2 trial assessing higher dosing at an 80KE dose (Cohort C) and systemic priming prior to initiation of intravesical administration (Cohort D). In addition, the Company intends to initiate a proof-of-concept study of TARA-002 in combination with pembrolizumab in NMIBC patients with CIS to assess the potential synergistic effects of the combination regimen. About TARA-002 TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of lymphatic malformations (LMs), for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432. When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-1b, IL-6, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and natural killer cells. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response. About Non-Muscle Invasive Bladder Cancer (NMIBC) Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle. About Protara Therapeutics, Inc. Protara is a clinical-stage biotechnology company committed to advancing transformative therapies for people with cancer and rare diseases. Protara’s portfolio includes its lead candidate, TARA-002, an investigational cell-based therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs). The Company is evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients with carcinoma in situ (CIS) who are unresponsive or naïve to treatment with Bacillus Calmette-Guérin (BCG), as well as a Phase 2 trial in pediatric patients with LMs. Additionally, Protara is developing IV Choline Chloride, an investigational phospholipid substrate replacement for patients on parenteral nutrition who are otherwise unable to meet their choline needs via oral or enteral routes. For more information, visit www.protaratx.com. References 1. Klinische Einheit, or KE, is a German term indicating a specified weight of dried cells in a vial. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Protara may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “designed,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words or expressions referencing future events, conditions or circumstances that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such forward-looking statements include but are not limited to, statements regarding Protara’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Protara’s business strategy, including its development plans for its product candidates and plans regarding the timing or outcome of existing or future clinical trials; statements related to expectations regarding interactions with the FDA; Protara’s financial position; statements regarding the anticipated safety or efficacy of Protara’s product candidates; and Protara’s outlook for the remainder of the year. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that contribute to the uncertain nature of the forward-looking statements include: risks that Protara’s financial guidance may not be as expected, as well as risks and uncertainties associated with: Protara’s development programs, including the initiation and completion of non-clinical studies and clinical trials and the timing of required filings with the FDA and other regulatory agencies; general market conditions; changes in the competitive landscape; changes in Protara’s strategic and commercial plans; Protara’s ability to obtain sufficient financing to fund its strategic plans and commercialization efforts; having to use cash in ways or on timing other than expected; the impact of market volatility on cash reserves; failure to attract and retain management and key personnel; the impact of general U.S. and foreign, economic, industry, market, regulatory, political or public health conditions; and the risks and uncertainties associated with Protara’s business and financial condition in general, including the risks and uncertainties described more fully under the caption “Risk Factors” and elsewhere in Protara's filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Protara undertakes no obligation to update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise, except as required by law. Company Contact: Justine O'MalleyProtara TherapeuticsJustine.OMalley@protaratx.com646-817-2836